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          Institute: MPI für medizinische Forschung     Collection: Abteilung Molekulare Neurobiologie     Display Documents

ID: 23109.0, MPI für medizinische Forschung / Abteilung Molekulare Neurobiologie
NMDA Receptor 2 (NR2) C-Terminal Control of NR Open Probability Regulates Synaptic Transmission and Plasticity at a Cerebellar Synapse
Translation of Title:NMDA Receptor 2 (NR2) C-Terminal Control of NR Open Probability Regulates Synaptic Transmission and Plasticity at a Cerebellar Synapse
Authors:Rossi, Paola; Sola, Elisabetta; Taglietti, Vanni; Borchardt, Thilo; Steigerwald, Frank; Utvik, Jo Kristian; Ottersen, Ole Petter; Köhr, Georg; D`Angelo, Egidio
Date of Publication (YYYY-MM-DD):2002-11-15
Title of Journal:Journal of Neuroscience
Journal Abbrev.:J. Neurosci.
Issue / Number:22
Start Page:9687
End Page:9697
Copyright:Copyright © 2002 Society for Neuroscience
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:The C-terminal domain of NMDA receptor 2 (NR2) subunits has been proposed to play a critical role in regulating NMDA receptor localization and function in postsynaptic densities. However, the mechanism of this regulation is not completely understood. In this paper we show that C-terminal truncation of NR2A and NR2C subunits in mice (NR2A/CC/C) impairs synaptic transmission and plasticity at the cerebellar mossy fiber-granule cell relay. Activation of synaptic NMDA receptors could be distinguished from that of extrasynaptic receptors by using the glutamate scavenger glutamate pyruvate transaminase and the open channel blocker MK801. NR2A/CC/C mice exhibited a specific reduction in synaptic NMDA receptor activation attributable to a severalfold decrease in channel open probability but not channel conductance. Immunodetection revealed normal developmental expression of NR subunit proteins. Quantitative immunogold analyses with an antibody to NR1 indicated that the reduction in receptor activation is not attributed to a reduced number of NR1-containing receptors in postsynaptic densities. Thus, NR2A/NR2C subunits and particularly their C termini regulate synaptic NMDA receptor activation and function by enhancing channel open probability, which is critical for long-term potentiation induction
Free Keywords:NMDA receptor; LTP; channel open probability; cerebellum; granule cell; gene knock-out
External Publication Status:published
Document Type:Article
Communicated by:Wulf Kaiser
Affiliations:MPI für medizinische Forschung/Abteilung Molekulare Neurobiologie
External Affiliations:Department of Molecular and Cellular Physiology and Istituto Nazionale per la Fisica della Materia, University of Pavia, I 27100 Pavia, Italy; Department of Evolutionary and Functional Biology, University of Parma, I-43100 Parma, Italy; Centre for Molecular Biology and Neuroscience, Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, N-0314 Oslo, Norway
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